Vantage Snippets are short summaries of breaking news stories.
Yesterday's green light for Axonics Modulation Technologies’ implanted sacral neuromodulator, r-SNM, for faecal incontinence is just the start for the product – the group expects a further US approval for urinary incontinence by the end of the year. The device stimulates the sacral nerves in the pelvic area, and is intended for patients who have failed on, or are unsuitable candidates for, drug therapy or other treatments. The device’s USP is that it can be recharged through the skin, which Axonics believes will allow it to carve out a niche from Medtronic. Medtronic’s Interstim devices, the first of which was approved in the US in 1997, is the main sacral nerve stimulator on the US market but cannot be recharged; when it runs out of juice it must be surgically removed and replaced. Axonics must make the most of this advantage: Medtronic plans to launch a rechargeable version of Interstim II in 2020. Neuromodulation devices continue to be approved or cleared by the FDA for a wide range of indications – the last two years have seen approvals for opioid withdrawal, heart failure and even cancer.
|Selected US neurostimulator approvals of the last two years|
|Device||Company||Type of stimulator||Indication||Date|
|r-SNM||Axonics Modulation Technologies||Sacral nerve stimulator||Faecal incontinence||Sep 9, 2019|
|Barostim Neo||CVRx||Carotid sinus nerve stimulator||Heart failure||Aug 16, 2019|
|IB-stim||Innovative Health Solutions||Non-implanted neurostimulator||Pain associated with IBS||Jun 7, 2019|
|NovoTTF-100L||Novocure||Low electric field tumour treatment||Cancer||May 23, 2019|
|Nerivio Migra||Theranica||Non-implanted neurostimulator||Migraine||May 20, 2019|
|Monarch||Neurosigma||Non-implanted neurostimulator||ADHD||Apr 19, 2019|
|Brainsway||Brainsway||Non-implanted neurostimulator||OCD||Aug 17, 2018|
|Cala One||Cala Health||Non-implanted neurostimulator||Upper limb tremor||Apr 26, 2018|
|TNM||Scion Neurostim||Non-implanted neurostimulator||Headache||Mar 26, 2018|
|Vercise||Boston Scientific||Deep brain stimulator||Parkinson’s symptoms||Dec 8, 2017|
|NSS-2||Innovative Health Solutions||Non-implanted neurostimulator||Opioid withdrawal||Nov 15, 2017|
|Source: EvaluateMedTech, company communications.|
Neurotrope joined the long list of Alzheimer’s disease disappointments this week with the failure of Bryostatin-1 in a mid-stage trial, wiping 77% – $42m – from the company’s market value. A look at cumulative market cap changes that can be attributed to news related to Alzheimer’s projects shows that there has been a huge desertion of investor support for the field this year. Vantage constructed this analysis from EvaluatePharma’s EventAnalyzer, which tracks the biggest share price moves among global biopharma companies each day. An important caveat to bear in mind here is that sentiment that built or declined slowly will not have been captured here. However the chart clearly shows how major events have triggered the various ebbs and flows of optimism over the past decade, and those following the Alzheimer’s field will not be surprised to see that this year is well into the red. Huge unmet need means that many investors will take positions in companies with skin in the game, for fear of missing out if the unexpected happens. But the field desperately needs to find a new way forward, as it is very hard to pinpoint projects that might prompt a recovery of the $39bn of market value that has eroded this year alone.
The 70% jump in Acadia Pharmaceutical’s shares this morning shows that few were expecting a positive readout from the Harmony study, testing Nuplazid in dementia-related psychosis. Only the top-line hit was announced: the trial was stopped early for efficacy after the drug demonstrated a “highly statistically significant” longer time to relapse of psychosis, compared with placebo. The magnitude of effect remains the big unknown here, and Acadia executives were tight-lipped on a call this morning, pending presentation of full data at a medical conference. Safety will also be important when these data emerge, as concerns have been raised in the past; all the company said today was that nothing surprising had been detected in Harmony. Acadia intends to approach the FDA next year about label expansion, and it remains to be seen whether approval will be possible on the back of a single study. Dementia-related psychosis represents a much bigger market – ten times bigger, according to the company – than Parkinson’s disease psychosis, in which Nuplazid is already approved, so the regulator is sure to proceed cautiously here. Nuplazid is forecast, according to EvaluatePharma consensus, to make $1.1bn in Parkinson’s psychosis alone in 2024. Investors seem convinced of the opportunity for now, with Acadia’s market cap ballooning by $2.2bn in early trade.
The molecular diagnostics group Opgen made a fairly dismal debut on the Nasdaq back in 2015, and has performed horribly since; its shares have lost 99.8% of their value since the IPO, and have gone through two major reverse stock splits. The Netherlands' Curetis, another diagnostics specialist, also floated in 2015, and has seen its share price drop a mere 93%. So today’s combination of these groups, neither of which is profitable, will have to work wonders to reverse these declines. The deal is structured as an all-share takeout of Curetis by Opgen: the US company will pay with 2.7 million new shares, and current holders will retain only a 27.5% ownership of the combined business. Opgen's stock is up 80% today, valuing Curetis at $32m, and the combined business at $44m. On a conference call today both management teams outlined plans to wring synergies from their combined operations – for example, the new group is to have 130 employees, whereas the two companies had a total of 166 at the end of 2018. The closing of the transaction is contingent on an interim equity financing, so this morning's share price surge is surprising.
Not having any clinical data under its belt has not stopped Achilles Therapeutics from closing a series B financing round that puts it in UK biotech’s all-time top five venture capital raises. While the company will not disclose the valuation at which today’s £100m ($120m) series B raise was done this will likely stand in the hundreds of millions of dollars, representing a huge uplift for Syncona, its founding investor. Syncona’s last disclosed stake in the company, 69%, was carried at a valuation of just $28m. Achilles focuses on the development of unmodified, expanded, autologous TILs (tumour-infiltrating lymphocytes) targeting clonal neoantigens, and has a lead project, ATL001, that recently started clinical trials in melanoma and non-small cell lung cancer. Knowing Syncona’s views on the public markets, and the fact that the series B round was led by a new US fund, RA Capital, there can be little doubt that a Nasdaq IPO is in the works for Achilles.
|The UK's biggest VC financings for UK biotech|
|Company||Investment ($m)||Date||Financing round|
|Orchard Therapeutics||150.0||Aug 2018||Series C|
|Freeline Therapeutics||123.9||Jun 2018||Series B|
|Achilles Therapeutics||119.9||Sep 2019||Series B|
|Mereo Biopharma||119.0||Jul 2015||Series A|
|Orchard Therapeutics||112.2||Dec 2017||Series B|
|Adaptimmune||104.0||Sep 2014||Series A|
|Archimedes Pharma||100.0||Mar 2010||Undisclosed|
|Kymab||100.0||Nov 2016||Series C|
From a total of 13 marketing decisions expected from the FDA, August saw eight approvals and three complete response letters. Notable regulatory nods included two Jak inhibitors: Abbvie’s rheumatoid arthritis drug Rinvoq and Celgene’s myelofibrosis therapy Inrebic; the latter was not included in Vantage's August PDUFA analysis as it had been due a decision in September. Both products came with label warnings that could limit their uses, namely thrombosis for Rinvoq and encephalopathy for Inrebic. Meanwhile, Sarepta got a knockback for its follow-on Duchenne therapy Vyondys 53, with the company citing the risk of infection at intravenous infusion ports and kidney toxicity. Important decisions due this month include the oral version of Novo Nordisk's GLP1 agonist semaglutide (Go or no go? Novo awaits call on oral sema, August 30, 2019).
|Notable first-time US approval decisions in August|
Product NPV ($m)*
|Turalio (pexidartinib)||Daiichi Sankyo||545||Approved||-|
|Wakix (pitolisant)||Harmony Biosciences||-||Approved||-|
|KPI-121||Kala Pharmaceuticals||1,650||CRL||US rejection knocks Kala off its Stride|
|Rozlytrek||Roche||1,017||Approved||Bayer could become the latest casualty of Roche’s targeted pricing|
|Vyondys 53 (golodirsen)||Sarepta||711||CRL||The Sarepta fairy tale takes a worrying turn|
|Xenleta (lefamulin)||Nabriva Therapeutics||456**||Approved||Nabriva gets a win, but investors are lukewarm|
|Rinvoq (upadacitinib)||Abbvie||10,595||Approved||Abbvie’s black box could be bad news for Galapagos and Gilead|
|Rexista/Oxycodone ER||Intellipharmaceutics International||112||No decision yet (adcom delay)||-|
|NKTR-181||Nektar Therapeutics||532||No decision yet (adcom delay)||-|
|Inrebic (fedratinib)***||Celgene||1,730||Approved||Celgene's myelofibrosis win represents an expensive green light|
|*NPV data from August 30; **includes both oral and IV versions; ***not noted in August story, PDUFA date September 3, 2019. Source: EvaluatePharma, Go or no go? Abbvie, Roche and Kala await key decisions.|
|Supplementary and other notable approval decisions in August|
|Hetlioz||Vanda Pharmaceuticals||sNDA for jet lag disorder||CRL|
|Sodium thiosulfate injection||Hope Pharmaceuticals||sNDA for chemotherapy-induced side effects||No decision yet|
Shareholders of both Olympus and Sony have applauded the latter group’s decision to sell its 5% Olympus stake for ¥80.4bn ($757m). Sony’s move follows campaigning by the activist investor Daniel Loeb’s hedge fund, Third Point, to get Sony to divest a number of assets, though the Japanese conglomerate insisted that the sale had not come in response to the activism. From Olympus’s point of view the deal falls in with its own plans; on Friday the company completed a separate buyback of ¥93bn-worth of its shares. Olympus’s stock price jumped 6% as a result, whereas Sony’s popped by 2%. The two groups’ joint venture, Sony Olympus Medical Solutions, will continue as before, having been formed in 2012 to develop high-definition surgical endoscopes and microscopes, at which point Sony bought an 11.5% stake in Olympus for $640m.
|Annual sales ($m)|
|Total medtech revenues||6,066||6,455||6,827||7,182||7,533||7,885||5%|
Pharnext’s hopes of a quick approval for its Charcot-Marie-Tooth disease project PXT3003 have been dashed by the US FDA. The agency’s request for a second phase III study of the asset could have been foreseen after formulation issues halted the high-dose arm of the previous trial, Pleo-CMT; this was the only dose to show a significant benefit on the primary and secondary endpoints. Still, Pharnext’s stock was down as much as 42% today, below its price when the company reported the first phase III data last October. Pharnext has not given details of the new trial’s design, but there must be worries about whether the group can complete it: Pleo-CMT took three years to yield data, and Pharnext had just €32m ($35m) in cash at the end of March. PXT3003, a combination of baclofen, naltrexone and sorbitol, is in a long-term follow-up study set to yield data later this year. The company is also seeking a fast approval for PXT3003 in Europe, but it now looks likely that regulators there will also request another study. According to EvaluatePharma the only other prominent project in clinical development for Charcot-Marie-Tooth disease is Acceleron’s ACE-083, which is in phase II.
Novartis’s plan to turn Arzerra from an underwhelming blood cancer drug into a less underwhelming one for multiple sclerosis is on track to deliver a US filing this year. This follows positive readouts today of Asclepios I and II, pivotal studies of Arzerra’s active ingredient, ofatumumab, showing reductions in annualised relapse rate versus Sanofi’s Aubagio in relapsing-remitting MS. Full data will be presented at next month’s Ectrims meeting, but Aubagio is a low bar to beat, having shown a 32% reduction in annual relapses. This has been blown out of the water by Roche’s blockbuster Ocrevus, which with an 80% reduction is Novartis’s real competitor. Ocrevus validated the anti-CD20 approach to treating MS, but ofatumumab is one of only three other MS projects using this mechanism. A second, TG Therapeutics’ ublituximab, is in the pivotal Ultimate-1 and 2 studies, which read out in 2021, and long-term follow-up from phase II will feature at Ectrims. Novartis has distinguished ofatumumab for MS from Arzerra by formulating it as a monthly SC injection, currently coded OMB157; 2024 forecast sales of OMB157 should easily beat Arzerra, according to EvaluatePharma, but will come nowhere close to those of Ocrevus.
|Anti-CD20 antibodies in development for MS|
|Project||Company||Status in MS||2024e sales in MS||Trial ID|
|Ocrevus||Roche||Approved for relapsing or PP MS||$6.7bn||NCT01194570|
|OMB157||Novartis/Genmab||Phase III in relapsing MS||$940m||NCT02792231
|Ublituximab||TG Therapeutics||Phase III in relapsing MS||$188m||NCT03277261
|BCD-132||Biocad||Phase I study in Russia||NA||NCT03551275|
|Rituxan||Roche||Failed Olympus trial in PP MS||Zero||NCT00087529|
|Source: EvaluatePharma; PP=primary progressive.|
Two deals in as many days featuring engineered T-cell receptors (TCRs) show that interest in this approach is alive and well, with companies able to command respectable sums for a technology that has yet to deliver any notable clinical breakthroughs. Immatics announced today that Celgene had handed over $75m up front for options over three research projects; the targets were not disclosed, though solid tumours are the focus. Celgene's cell therapy focus, via its Juno acquisition, has mainly been on CAR-T, though it has one TCR project in the clinic; Bristol-Myers Squibb has said that a key reason why it wanted to buy Celgene was to gain a foothold in cell therapy, and the big pharma group has presumably signed off on this transaction, though Immatics declined to confirm that. Yesterday, the UK’s Adaptimmune unveiled a collaboration with Noile-Immune Biotech to develop TCRs that co-express IL-7 and CCL19, also aiming at solid tumours; the deal is worth up to $312m to the Japanese company. Adaptimmune is arguably one of the leaders in this field, but its work has been blighted by patient deaths; perhaps this deal is an acknowledgement that its technology needs a tweak.
|Selected engineered TCR projects|
|Adaptimmune||MAGE-A10 TCR||MAGE A10 (deprioritised Aug 2019)||Phase I||NCT02592577|
|MAGE-A4 TCR||MAGE A4 (linked to one patient death)||Phase I||NCT03132922|
|AFP TCR||Alpha-fetoprotein||Phase I||NCT03132792|
|Gilead||KITE-718||MAGE A3/A6||Phase I||NCT03139370|
|KITE-439||HPV-16 E7||Phase I||NCT02858310|
|KRAS TCR||G12V variant of mutated RAS||Phase I||NCT03190941|
|NCI (NIH)||HPV-16 E6 TCR||HPV-16 E6||Phase I||NCT03197025|
|MAGE A3 TCR||MAGE A3||Phase I||NCT02153905|
|Bellicum||BPX-701||PRAME (rimiducid-activated suicide switch)||Phase I||NCT02743611|
|Cell Medica||CMD-602||WT-1||Phase I||NCT02550535|
|Tmunity||NYCE T cells||NY-ESO-1 (Crispr-edited, TCR-deleted, PD-1-deleted)||Phase I||NCT03399448|
|Medigene/Bluebird||None||Six undisclosed targets||Preclinical||NA|
|Regeneron/Adicet Bio||None||Undisclosed targets for allogeneic use||Preclinical||NA|
|Regeneron/Bluebird||None||Six undisclosed targets||Preclinical||NA|
|*Licensed from Adaptimmune. Source: company filings & clinicaltrials.gov.|